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The Three-Dimensional NMR Solution Structure of α-Cobratoxin at pH 7.5 and Conformational Differences With the NMR
Eric Leroy1, Afaf Mikou, Yinshan Yang
1a Laboratoire de Résonance Magnétique Nucléaire Institut de Chimie des Substances Naturelles Centre National de la Recherche Scientifique , 91190 , Gif-sur-Yvette , France.
Abstract:
Abstract The 3D solution structure of α-cobratoxin, a neurotoxin purified from the Naja naja siamensis snake venom, has been determined by Nuclear Magnetic Resonance spectroscopy, in conjunction with distance geometry and restrained molecular dynamics, at pH 7.5. A total of 490 distance restraints were obtained from NOE intensities and 25 φ dihedral angle restraints deduced from J- coupling data. The generated structures are well defined with root mean square deviations from a geometrical mean structure of 0.107 ± 0.036 nm for the backbone atoms and 0.128 ±0.073 nm for the side-chain atoms (considering residues 1 to 66 minus 26 to 35). A comparison between the generated structures at pH 7.5 and the mean NMR solution structure at pH 3.2 revealed that the 3D structure of α-cobratoxin is more compact at neutral pH. This major difference is mainly due to the pH-dependant conformational variations of three residues His(18), Thr(44) and Thr(59).
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